Peritoneal Surgery and Intraperitoneal Chemotherapy | Mesothelioma Applied Research Foundation

Peritoneal Mesothelioma

Cytoreductive Surgery and
Intraperitoneal Chemotherapy

Garrett Nash MD, MPH
Assistant Attending Surgeon
Memorial Sloan-Kettering Cancer Center
September 28th, 2012


About me
• Training in Colorectal Surgery and
Surgical Oncology
• Peritoneal based diseases
– Appendix Cancer
– Metastatic Colorectal Cancer
– Peritoneal Mesothelioma


• What is the disease?
• What are the surgical options?
• What are the outcomes after surgery?


• 2nd most common site of mesothelioma is the
peritoneum
– 10-30% of cases of mesothelioma
– 300-400/cases in U.S. year


Background
• Causes
– Asbestos exposure
– Simian virus-40
– Radiation
– Chronic inflammation of the peritoneum
• Presentation
– Increased abdominal girth
– Ascites (fluid in the abdomen)
– Abdominal pain
– Weight loss


Treatment Options
• “Traditional”
– Chemotherapy (doxorubicin and cisplatin)
– Radiation
– Drainage of abdominal fluid to alleviate pressure
(palliative paracentesis)
– Surgical excision of some of the tumor to alleviate
intestinal blockage (palliative debulking)


Annals of Oncology 18:827-834, 2007


Surgical Options
• Cytoreductive surgery (CRS) and perioperative
intraperitoneal chemotherapy (IPC)
– Surgical cytoreduction to eliminate visible disease
by destroying tumor (burning/peeling/wiping) or
removing organs
– Delivery of chemotherapy directly to the
peritoneal surfaces to eliminate microscopic
disease


• EPIC – Early Postoperative Intraperitoneal
Chemotherapy
– Taxol/5FU

• HIPEC – Hyperthermic (heated)
– Cisplatin/Doxorubicin/Mitomycin C


Management of Ovarian Cancer
415 patients with peritoneal metastasis were randomized
1. Intraperitoneal chemotherapy (post operative)
2. Intravenous chemotherapy after cytoreductive surgery

Gynecologic Oncology Group. N Engl J Med. 2006.5;354:34-43.


Management of Colorectal Cancer
105 patients with peritoneal metastasis were randomized
1. Intravenous chemotherapy
2. Cytoreductive surgery + intraperitoneal chemo + intravenous
chemo

CRS + IPC + IVC

IVC

Verwaal. J Clin Oncol. 2003;21(20):3737-43.


• Review of cytoreductive surgery and IPC
• 7 non randomized studies
• 240 patients


Inclusion Criteria Exclusion Criteria
• Histological diagnosis of • Surgical debulking without IPC
diffuse malignant peritoneal • Studies that mix in other
mesothelioma (DMPM) cancer types
• Patients undergoing
cytoreductive surgery (CRS) +
intraperitoneal chemo (IPC)



Survival after CRS with IPC



Survival after CRS with IPC

• Range of average survival by study: 3-7 years



Complications and Mortality after
Cytoreductive Surgery and IPC
• Average length of operation 6-10 hours
• Average hospital length of stay 16 days
• Surgical complication rate 25-40%
• Hematological toxicity 8-26%
• Perioperative mortality 0-8%



How can we predict prognosis?
• No widely accepted staging system for
peritoneal mesothelioma
• No information on National Cancer Institute
website (cancer.gov)


• 8 institutions prospective collected data
• 294 patients treated with cytoreductive
surgery and intraperitoneal chemotherapy

Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63


• Primary objective: Formulate a staging
system through identification of prognostic
factors.



Patient Factors
Associated with Survival



Pathology/Surgery Factors
Associated with Survival



Classification of Peritoneal
Mesothelioma
• 3 histological subtypes
– Epithelial
– Sarcomatoid
– Mixed/biphasic
Sarcomatoid
Epithelial


Peritoneal cancer index (PCI)

• During surgery
• Tumor distribution (13 abdominal pelvic regions)
•Tumor nodule size (0-3 points)


Optimal Cytoreductive Surgery
Residual visible tumor nodules
• CC0 - none
• CC1 - <2.5mm
• CC2 - 2.5 mm-2.5cm
• CC3 - >2.5cm


TNM staging system
• Most common system used for staging cancer
• T stage – size or depth of tumor (1-4)
• N stage – presence of lymph nodes with cancer (0-2)
• M stage – presence of metastasis to organs (0- 1)


TNM staging system
• Most common system used for staging cancer
• T stage – size or depth of tumor (1-4)
• N stage – presence of lymph nodes with cancer (0-2)
• M stage – presence of metastasis to organs (0- 1)

• For colon cancer
• Stage I = T1/2, N0, M0
• Stage II = T3/4, N0, M0
• Stage III = N1/2, M0
• Stage IV = M1


Survival Stratified by T Stage
Based on PCI
• T1 = PCI 1-10
• T2 = PCI 11-20
• T3 = PCI 21-30
• T4 = PCI 30-39



Survival Stratified by Nodal Stage



Survival Stratified by M stage
• M1 = extraabdominal
disease (e.g. chest/skin)



Overall survival stratified by
TNM staging system
52 patients
T1 N0 M0
166 patients

T2-3 N0 M0
76 patients

T4 or N1 or M1



Combining TNM Stage
with Histology and Optimal Surgery

HR CI
Sarcomatoid vs. epitheloid 5.5 2.9-10.5
Incomplete vs. complete CRS 2.0 1.2-3.2
Stage II vs. I 3.3 1.2-9.4
Stage III vs. I 5.9 2.1-17.2



Summary
• Appears to stratify patients for prognosis
– Patients who do poorly
• High volume disease
• Extra-abdominal disease
• Non-epitheloid histology
– Patients who do ‘well’
• Low volume disease
• Node negative
– Selected patients undergoing CRS


Conclusions
• Surgery offers good long term outcomes
for selected patients with favorable
tumors
• Surgery is high risk
• We need comparative studies that
demonstrate how much surgery and
intraperitoneal chemotherapy may
benefit patients


Thank You
• Mesothelioma Applied Research
Foundation and Lee Krug, MD


Thank You
• My medical oncology collaborator,
Andrea Cercek, MD


Thank You
• My medical oncology collaborator,
Andrea Cercek, MD
• The patients who allow us to study their
tumors

Peritoneal Surgery and Intraperitoneal Chemotherapy | Mesothelioma Applied Research Foundation

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